PDBsum entry 2jj9

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Contractile protein PDB id
Protein chain
692 a.a. *
Waters ×508
* Residue conservation analysis
PDB id:
Name: Contractile protein
Title: Crystal structure of myosin-2 in complex with adp- metavanadate
Structure: Myosin-2 heavy chain. Chain: a. Fragment: motor-domain, residues 2-761. Synonym: myosin-2, myosin ii heavy chain
Source: Dictyostelium discoideum. Slime mold. Organism_taxid: 44689
2.30Å     R-factor:   0.225     R-free:   0.275
Authors: R.Fedorov,M.Boehl,G.Tsiavaliaris,F.K.Hartmann,P.Baruch, B.Brenner,R.Martin,H.J.Knoelker,H.O.Gutzeit,D.J.Manstein
Key ref:
R.Fedorov et al. (2009). The mechanism of pentabromopseudilin inhibition of myosin motor activity. Nat Struct Biol, 16, 80-88. PubMed id: 19122661 DOI: 10.1038/nsmb.1542
25-Mar-08     Release date:   13-Jan-09    
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Protein chain
Pfam   ArchSchema ?
P08799  (MYS2_DICDI) -  Myosin-2 heavy chain
2116 a.a.
692 a.a.
Key:    PfamA domain  Secondary structure

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     myosin complex   1 term 
  Biochemical function     ATP binding     2 terms  


DOI no: 10.1038/nsmb.1542 Nat Struct Biol 16:80-88 (2009)
PubMed id: 19122661  
The mechanism of pentabromopseudilin inhibition of myosin motor activity.
R.Fedorov, M.Böhl, G.Tsiavaliaris, F.K.Hartmann, M.H.Taft, P.Baruch, B.Brenner, R.Martin, H.J.Knölker, H.O.Gutzeit, D.J.Manstein.
We have identified pentabromopseudilin (PBP) as a potent inhibitor of myosin-dependent processes such as isometric tension development and unloaded shortening velocity. PBP-induced reductions in the rate constants for ATP binding, ATP hydrolysis and ADP dissociation extend the time required per myosin ATPase cycle in the absence and presence of actin. Additionally, coupling between the actin and nucleotide binding sites is reduced in the presence of the inhibitor. The selectivity of PBP differs from that observed with other myosin inhibitors. To elucidate the binding mode of PBP, we crystallized the Dictyostelium myosin-2 motor domain in the presence of Mg(2+)-ADP-meta-vanadate and PBP. The electron density for PBP is unambiguous and shows PBP to bind at a previously unknown allosteric site near the tip of the 50-kDa domain, at a distance of 16 A from the nucleotide binding site and 7.5 A away from the blebbistatin binding pocket.
  Selected figure(s)  
Figure 1.
(a) Effect of PBP on the steady-state actin-activated ATPase activitiy of Dd myosin-5b. Actin-activated ATPase activities in the absence ( square ) and presence of 25 M PBP ( down triangle ) are shown. (b) Concentration-dependence of the inhibition of the actin-activated ATPase activity of different myosin isoforms in the presence of 0–150 M PBP. The semilogarithmic plot shows the concentration dependence for myosin-1E (o), myosin-2 ( square ), Dd myosin-5b ( ) and chicken myosin-5a ( down triangle ). The concentrations of PBP required for half-maximal inhibition (IC[50]) of the different myosin motors were determined from sigmoidal fits of the data. All parameters are summarized in Table 1. (c) Fluorescence transients obtained upon mixing 1 M Dd myosin-5b with 10 M mantATP in the absence and presence of 5 M, 25 M, 50 M and 100 M PBP. The concentration dependence of the amplitude of the fast phase is shown in the inset. (d) Rate constants for ATP binding and hydrolysis were determined by following the time-dependent changes in the intrinsic protein fluorescence of Dd myosin-5b. Addition of 25 M PBP leads to a 14-fold reduction in the apparent second-order rate constant for ATP binding and a ten-fold reduction of the rate of ATP hydrolysis (Supplementary Methods online). (e) PBP-mediated inhibition of chicken myosin-5a in the in vitro motility assay. The histograms show the average sliding velocity of rhodamine-phalloidin–labeled actin filaments in the absence and presence of 10 M PBP.
Figure 3.
Myosin residues interacting with PBP are shown as predicted by molecular modeling for Dd myosin-1E (a), Sc Myo2 (b), Gg myosin-5a (c) and Dd myosin-5b (d).
  The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Biol (2009, 16, 80-88) copyright 2009.  
  Figures were selected by an automated process.